P24: Maternal melatonin administration for prevention of fetal lung injury induced by intrauterine inflammation and for fetal lung maturation

The physiological development and homeostasis of the lung alveolus is determined by the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) by the interstitial lipofibroblast. We have recently shown (Dasgupta C et al., Am J Physiol Lung Cell Mol Physiol 296: L1031–L1041, 2009.) that PPAR-γ agonists administered postnatally accelerate lung maturation and prevent hyperoxia-induced lung injury. However, whether the same occurs antenatally is not known. The objective of this study was to test the hypothesis that the potent PPAR-γ agonist rosiglitazone (RGZ), administered antenatally, enhances fetal lung maturation and protects against hyperoxia-induced neonatal lung injury. Sprague-Dawley rat dams were administered either diluent or RGZ (3 mg/kg), at late gestation, to determine its effect on lung maturation and on hyperoxia (95% O2 exposure for 24 h)-induced neonatal lung injury. The lungs were examined for the expression of specific markers of alveolar development (surfactant proteins A and B, cholinephosphate cytidylyltransferase-α, leptin receptor, triglyceride uptake, and [3H]choline incorporation into saturated phosphatidylcholine) and injury/repair, in particular, the markers of transforming growth factor-β signaling (activin receptor-like kinase-5, SMAD3, lymphoid enhancer factor-1, fibronectin, and calponin). Overall, antenatal RGZ accelerated lung maturation and blocked the inhibition of alveolar sacculation and septal wall thinning by hyperoxia. RGZ specifically stimulated the development of the alveolar epithelial type II cell, the lipofibroblast, and the vasculature. The increased expression of the transforming growth factor-β intermediates, such as SMAD3 and lymphoid enhancer factor-1, implicated in hyperoxic lung injury, was also blocked by antenatal RGZ treatment. In conclusion, PPAR-γ agonists can enhance fetal lung maturation and can effectively prevent hyperoxia-induced neonatal lung injury.

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Faculty of 1000 evaluation for Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.718089952.793484597 ◽

2013 ◽

Author(s):

Monika Gappa

Keyword(s):

At Risk ◽

Preterm Birth ◽

Fetal Lung ◽

Lung Maturation ◽

Fetal Lung Maturation

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Faculty Opinions recommendation of Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727428659.793572655 ◽

2020 ◽

Author(s):

Katie-Jane Wynne

Keyword(s):

At Risk ◽

Preterm Birth ◽

Fetal Lung ◽

Antenatal Corticosteroids ◽

Lung Maturation ◽

Fetal Lung Maturation

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The cellular mechanism of glucocorticoid acceleration of fetal lung maturation. Fibroblast-pneumonocyte factor stimulates choline-phosphate cytidylyltransferase activity.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)35914-8 ◽

1986 ◽

Vol 261 (5) ◽

pp. 2179-2184 ◽

Cited By ~ 2

Author(s):

M Post ◽

A Barsoumian ◽

B T Smith

Keyword(s):

Fetal Lung ◽

Cellular Mechanism ◽

Lung Maturation ◽

Choline Phosphate ◽

Fetal Lung Maturation

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Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation

Pediatric Research ◽

10.1038/s41390-021-01489-4 ◽

2021 ◽

Author(s):

Erin V. McGillick ◽

Sandra Orgeig ◽

Beth J. Allison ◽

Kirsty L. Brain ◽

Youguo Niu ◽

...

Keyword(s):

Vitamin C ◽

Lung Development ◽

Fetal Lung ◽

Late Gestation ◽

Lung Maturation ◽

Maternal Vitamin ◽

Healthy Pregnancy ◽

Daily Vitamin ◽

Expression Of Genes ◽

Fetal Lung Maturation

Abstract Background In the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown. Methods We investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105–138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry. Results Maternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1, hypoxia signaling genes (HIF-2α, HIF-3α, ADM, and EGLN-3), genes regulating sodium movement (SCNN1-A, SCNN1-B, ATP1-A1, and ATP1-B1), surfactant maturation (SFTP-B and ABCA3), and airway remodeling (ELN). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue. Conclusions Maternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy. Impact Maternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development. Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth. In the future, the availability/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.

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